Gender	Male
E-mail	hugo.vega@mssm.edu
Education and Training	M.D., Universidad Nacional de Columbia
	M.Sc., Universidad Nacional de Columbia
	Ph.D., Osaka University
	Postdoctoral Fellowship, Johns Hopkins University

Education and Training	M.D., Universidad Nacional de Columbia
	M.Sc., Universidad Nacional de Columbia
	Ph.D., Osaka University
	Postdoctoral Fellowship, Johns Hopkins University

Cell proliferation and embryo development

I am interested in the role that cellular proliferation plays on embryo development using Roberts syndrome as a model. RBS is a developmental recessive disease characterized by phocomelia and craniofacial abnormalities including microcephaly. At the cellular level, RBS presents lack of cohesion at the heterochromatic regions around centromeres. Using positional cloning we determined that RBS is caused by mutations in ESCO2, which encodes a protein belonging to the Eco1 family of acetyltransferases that is involved in the establishment of sister chromatid cohesion in S phase.

 

One of our research aims is to elucidate the role of ESCO2 in the process of sister chromatid cohesion and how this process is regulated. To address these issues we have used protein chips to perform global analysis of ESCO2 protein-protein interactions. This approach will allow the delineation of pathways involved in the regulation of cohesion as well as networks incorporating these and other pathways implicated in cell cycle control, DNA replication, recombination, and repair. We have applied this proteomic approach to the study of other members of the Eco1 family in humans and yeasts because this will enhance our understanding of the essential and conserved mechanisms underlying the function of these proteins.

 

We also aim to understand how cohesion defects affect cell proliferation and how cell proliferation efficiency impacts the brain and body size and patterning of face, limb, hearth and kidney during development. We have established a number of cell lines from RBS patients bearing different types of ESCO2 mutations that allowed us to determine that loss of ESCO2 acetyltransferase activity contributes significantly to the pathogenesis of RBS. In addition, we found that RBS cells have decreased proliferation capacity that is associated with cell death but not with increased cell cycle duration. We have proposed that these proliferation defects may lead to the development defects in RBS. Currently our laboratory is implementing mouse models of RBS that will allow us to test our hypothesis about the role of cell proliferation in the pathogenesis of RBS. These mouse models will also help us to explore the relation between cell cycle control and the developmental pathways that contribute to brain and body size and patterning of face, limb, hearth and kidney during development.

Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, Kayserili H, Basaran S, Skovby F, Hennekam RC, Uzielli ML, Schnur RE, Manouvrier S, Chang S, Blair E, Hurst JA, Forzano F, Meins M, Simola KO, Raas-Rothschild A, Schultz RA, McDaniel LD, Ozono K, Inui K, Zou H, Jabs EW. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity. Hum Mol Genet 2008 Apr 14;.

Gordillo M, Vega H, Sakai N, Tsukamoto H, Ozono K, Koji I. Characterization of the sensitivity to various stress agents in Roberts syndrome lymphoblastoid cell lines. Medical Journal of Osaka University 2006; 49: 29-41.

Wilches R, Vega H, Echeverry O, Barrera LA. Colombian haplotypes of the Gaucher disease-causing N370S mutation may originate from a possible common ancestral haplotype. Biomedica 2006; 26: 434-441.

Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, van Gosliga D, Kayserili H, Xu C, Ozono K, Jabs EW, Inui K, Joenje H. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nat Genet 2005; 37: 468-470.

Kato Z, Fukuda S, Tomatsu S, Vega H, Yasunaga T, Yamagishi A, Yamada N, Valencia A, Barrera LA, Sukegawa K, Orii T, Kondo N. A novel common missense mutation G301C in the N/acetylgalactosamine/6/sulfate sulfatase gene in mucopolysaccharidosis IVA. Hum Genet 1997; 101: 97-101.

Echeverry O, Barrera LA, Bermudez M, Vega H, Espinoza E. Mucopolysaccharidosis 1H (Hurler Syndrome). First cases in Colombia. Colombia Medica 1995; 26: 89-92.